Analysis of the embryonic development of the brain in Drosophila melanogaster

• Applicant: Dr. Rolf Urbach
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2009 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 125994177

Deciphering the mechanisms that control the generation of different cell types in the brain is one of the major challenges in developmental biology. This research proposal is intended to contribute to an understanding of the early processes underlying the development of the brain in the fruit fly Drosophila. Using genetic and experimental approaches, the mechanism regulating the generation of neural cell diversity will be clarified at the level of identified cells. Towards this aim we could already follow the formation of all neural stem cells (neuroblasts) in the embryonic brain, and individually identified them by means of specific molecular markers. On the basis of these data we recently deciphered a regulatory network of evolutionarily highly conserved transcription factors that regionalizes the early brain in dorsoventral axis. Our data demonstrated that subdivision of the neuroectoderm into discrete domains of DV gene activity is essential for the formation and fate specification of brain neuroblasts and ultimately controls the proper production of neural cell types. A first main aim of this research project is, therefore, to continue our former studies on patterning the embryonic brain. It is intended to proceed the investigations on the regulatory interactions between DV genes and on their regulation by potential upstream factors. We also will clarify the role of other evolutionarily conserved genes (e.g. cephalic gap genes and genes of the `retinal determination network´) within our gene regulatory network underlying brain patterning. The second main object of this proposal is to continue our investigations on the development of the cell lineages of the mushroom bodies, which are brain structures essentially for olfactory learning and memory. Recently, we uncovered the origin of the mushroom body neuroblasts and could show that each embryonic neuroblast generates an individual cell lineage comprising different numbers and types of neurons. Our detailed knowledge about those lineages now facilitates to resolve the cellular, genetic, and molecular mechanisms underlying their development and differentiation at the level of identified neuroblasts and daughter cells. It is intended to link individual embryonic and postembryonic cell lineages, and starting from genetic factors that we recognized to be differentially expressed in the embryonic cell lineages, we will analyse the mechanisms that determine the individual identity and proliferation capacity of the mushroom body neuroblasts and lead to the clone-specific differences in their cell lineages. Deciphering the regulatory interactions of evolutionarily conserved developmental control genes in brain development of the fruit fly, as designed in this proposal, will also be used for a phylogenetical comparison, and finally, may help to better understand patterning and generation of cell diversity in the brain of vertebrates.

• DFG Programme: Research Grants